Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages
Details
Publication Year 2024-12-04,Volume 15,Issue #1,Page 10556
Journal Title
Nature Communications
Abstract
New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. In this manuscript we characterize 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv-exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target. We show that humAb 826827 blocks the invasion of human reticulocytes using Pv clinical isolates and inhibits sporozoite invasion of human hepatocytes in vitro (IC(50) of 0.3 - 3.7 µg/mL). Inoculation of human liver transgenic (FRG-humHep) female mice with humAb 826827 significantly reduces liver infection in vivo. The crystal structure of rPvAMA1 bound to 826827 shows that 826827 partially occupies the highly conserved hydrophobic groove in PvAMA1 that binds its known receptor, RON2. We have isolated a potent humAb that is isolate-transcendent, blocks both pre-erythrocytic and blood stage infection, and could be a potential therapy for Pv.
Publisher
Springer Nature
Keywords
*Plasmodium vivax/immunology; Animals; Humans; *Protozoan Proteins/immunology/metabolism/chemistry/genetics; *Malaria, Vivax/immunology/parasitology/drug therapy; *Antigens, Protozoan/immunology/metabolism; *Antibodies, Monoclonal/immunology/pharmacology; Female; *Membrane Proteins/immunology/metabolism; Mice; *Mice, Transgenic; Hepatocytes/parasitology/immunology/metabolism; Antibodies, Protozoan/immunology; Sporozoites/immunology; Reticulocytes/parasitology/metabolism/immunology; Erythrocytes/parasitology/immunology; Leukocytes, Mononuclear/immunology; Liver/parasitology
Research Division(s)
Infectious Diseases And Immune Defence
PubMed ID
39632799
Open Access at Publisher's Site
https://doi.org/10.1038/s41467-024-53848-4
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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